Cohort study of fatty acid synthase expression and patient survival in colon cancer.
OBJECTIVE
Energy balance seems to be important in the pathogenesis of colon cancer. Fatty acid synthase (FASN) is physiologically regulated by energy balance and is often upregulated in colorectal cancer. Nonetheless, the influence of FASN expression on patient outcome is uncertain.


METHODS
Using the database of 647 patients with colon cancer in two independent cohort studies, FASN overexpression was detected in 84 tumors (13%) by immunohistochemistry. Cox proportional hazards models calculated hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related tumoral features, including KRAS, BRAF, p53, microsatellite instability and the CpG island methylation phenotype.


RESULTS
There were 279 deaths, including 160 colon cancer-specific deaths. FASN overexpression was associated with a significant reduction in colon cancer-specific mortality by both univariate and multivariate analyses (adjusted HR, 0.41; 95% CI, 0.19 to 0.89) and an insignificant trend toward improved overall mortality (adjusted HR, 0.75; 95% CI, 0.50 to 1.13). Notably, the effect of FASN expression on mortality might be different according to body mass index (BMI; P(interaction) = .019); the adjusted HR of overall mortality for FASN overexpression was 0.63 (95% CI, 0.39 to 1.02) among patients with BMI less than 27.5 kg/m(2) and 2.91 (95% CI, 1.19 to 7.12) among those with BMI >or= 27.5 kg/m(2). Moreover, the adverse effect of moderate overweight/obesity on overall survival was limited to FASN-positive tumors (adjusted HR, 4.10; 95% CI, 1.14 to 14.8; BMI >or= 27.5 kg/m(2) v < 27.5 kg/m(2)). CONCLUSION Among nonobese patients with colon cancer, tumoral FASN overexpression is associated with improved survival, whereas among moderately overweight or obese patients (BMI >or= 27.5 kg/m(2)), FASN overexpression may predict a worse outcome.
Ogino
Shuji
S
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. shuji_ogino@dfci.harvard.edu
Nosho
Katsuhiko
K
Meyerhardt
Jeffrey A
JA
Kirkner
Gregory J
GJ
Chan
Andrew T
AT
Kawasaki
Takako
T
Giovannucci
Edward L
EL
Loda
Massimo
M
Fuchs
Charles S
CS
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015992:Body Mass Index; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D054890:Fatty Acid Synthase, Type I / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I